Samarium-catalyzed Asymmetric Radical Transformations

ended

Complex biologically-active molecules, containing linked rings of atoms and possessing elaborate 3D forms, represent the ultimate challenge for synthetic chemists. As many of society’s established and future drugs, agrochemicals, and biological probes, boast intricate architectures, the ability to efficiently generate molecular complexity from simple starting materials is vital. Radical cyclization cascade reactions could well provide the solution; they have the potential to deliver complex architectures, with control of three dimensional shape, in one-step. Unfortunately, carrying out reactions with radicals in an enantiocontrolled fashion remains challenging due to their high reactivity. This is particularly the case for radicals generated using the classical reagent, samarium(II) diiodide (SmI2). SmI2 is one of the global community’s most important and widely used reagents for radical chemistry, as evidenced by its commercial availability and its pivotal use in numerous scientific studies around the world. Despite over 40 years of widespread use, and 1000s of publications describing its chemistry, two well-known disadvantages shadow SmI2: 1. An inability to control the enantioselectivity of radical reactions using SmI2, and; 2. The requirement for the use of a significant stoichiometric excess of SmI2 thus raising issues of cost and waste. Bringing together the Procter group’s recent breakthroughs in chiral ligand control and catalysis using SmI2, Dr Agasti’s ‘SmART’ project will develop the first catalytic enantioselective reactions using SmI2. Furthermore, the new catalytic processes will be used to convert simple feedstocks into high-value, complex, cyclic molecules bearing multiple stereocenters with high enantio- and diastereocontrol. Previously, such molecules could only be prepared by laborious multi-step synthesis. Dr Agasti’s approach will therefore streamline complex molecule synthesis, saving time and money, and minimizing chemical waste.